Evidence of possible dose-dependent doxorubicin plasma kinetics in man.

Abstract

The published plasma clearance profiles of doxorubicin in man (with differing liver status) have been analyzed further using a kinetic model instead of a linear regression model. At high (60 mg/m2 and 45 mg/m2) and intermediate (30 mg/m2) doxorubicin dose levels, a triphasic drug clearance pattern is apparent. However, at a low dose level (15 mg/m2), a biphasic profile can adequately describe the kinetics. This association of the kinetics with drug dose has been demonstrated in several ways, the simplest of which involves graphic overlaying of juxtaposed plasma clearances, and shows the emergence of a kinetic profile for low dose levels that is markedly different from that at high dose level..